In vitro cell models for cervical cancer have been developed. Immortalized cell lines were obtained using recombinant human papillomavirus (HPV) associated with cancer. Squamous cell carcinomas were produced. Thus, it is possible to study the regulation of immortalization and the mechanisms for progression to malignancy. The possible importance of cofactors, other viruses, chemical carcinogens, and oncogenes for cervical cancer is being explored. Herpes simplex 2 studies have been extended utilizing subfragments of a subgenomic region of herpes. A number of cell lines containing a specific subfragment of the morphological transforming region (Bgl II N) have maintained the integrated HPV genome and the herpes fragment over 20 subpassages. Because infected cervical cells pass through premalignant stages, markers are needed to facilitate the recognition of malignancy. A number of spontaneous and experimentally induced carcinomas of the cervix were characterized by a cytoskeletal qualitative change. All tumors lacked keratin 14 which is found in normal and HPV immortalized cell lines. Therefore, it is possible that the loss of keratin 14 is a general marker for cervical cancer. The epidermal growth factor receptor family is being examined in detail because the epithelial cells have them. Foreskin immortalized by HPV-16 keratinocytes were converted to malignant cells that produced squamous cell carcinomas by delta Nerb B2. These cells continue to express the HPV sequences. Thus, this multistage model utilizing human cells indicates that in continuous expression of HPVs, property of spontaneous cancer is also found in cancers that are experimentally produced.